Abstract 3426
Background
Subgroup analyses of randomized, controlled trials (RCTs) using high dose chemotherapy (HD) with autologous stem cell support (autoSCT) reveal a potential benefit of HD in patients with triple negative breast cancer (TNBC) and in tumors harboring features of HRD (Vollebergh et al, 2011). The phase III part of the neo-TN RCT, compared neo-adjuvant HD with conventional treatment (CONV) in BRCA1-like TNBC.
Methods
Patients with cT2-3N0-3M0 TNBC with HRD were randomized between HD or CONV after 3 courses of 2-weekly doxorubicin/cyclophosphamide (ddA60C600). CONV treatment consisted of another 3xddAC, or in case of an unfavorable response on MRI a switch to 3 cycles capecitabine800BID14-7/docetaxel75; after an amendment all patients switched to 3xcarboplatinAUC6/paclitaxel80weekly. The HD regimen consisted of a 4th course ddAC and 2 courses of cyclophosphamide3000d1/carboplatin400d1,2/ thiotepa250d2 both followed by autoSCT. Primary outcome was the Neo-adjuvant Response Index (NRI), secondary outcomes included overall (OS) and recurrence free survival (RFS).
Results
From 2010 to 2016, 122 patients were randomized (intention-to-treat). Median follow-up is 45 months. There was no significant difference in NRI between HD and CONV (mean NRI 0.78 versus 0.72, range 0-1, p = 0.41 Wilcoxon test). An NRI of > 0.7 was strongly associated with good prognosis (RFS of 97% [95%CI 93%-100%] versus 67% [95%CI 55%-82%] at 4 years). See Table for 4-years OS and RFS comparing HD with CONV. There were no treatment related deaths. However, 7 out of 55 patients who actually received HD did not complete HD mainly because of infections or allergic reactions.Table:
187P
HD % (95%CI) | CONV % (95%CI) | HR (95%CI) | p-value | |
---|---|---|---|---|
All (n = 122) | ||||
4-yrs OS 4-yrs RFS | 92 (85-99) 92 (85-99) | 79 (69-91) 78 (68-89) | 0.43 (0.15-1.23) 0.41 (0.15-1.07) | 0.12 0.07 |
Stage III only (n = 35) | ||||
4-yrs OS | 93 (81-100) | 60 (39-93) | 0.14 (0.02-1.14) | 0.07 |
Conclusions
No significant efficacy differences were found between HD and CONV. The NRI is of prognostic value. Whether the HD regimen is promising, especially in very high risk BRCA1-like TNBC [HR = 0.14], requires additional data including a comparison with platinum treatment in all control arm patients.
Clinical trial identification
NCT01057069.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The Dutch Cancer Foundation (KWF) and by the Schumacher Kramer Foundation.
Disclosure
S.C. Linn: Research grant / Funding (self), research support for patients fees in D-Care study: Amgen; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Cergentis; Research grant / Funding (self): Genentech; Advisory / Consultancy: IBM; Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (institution), patients fees in TEAM 2b study: Pfizer; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Roche; Research grant / Funding (institution): Tesaro; Speaker Bureau / Expert testimony, Fee for teaching, paid to institution: Bayer. All other authors have declared no conflicts of interest.
Resources from the same session
3971 - Unravelling the biological characteristics of MammaPrint extreme risk subgroups
Presenter: Rajith Bhaskaran
Session: Poster Display session 2
Resources:
Abstract
5871 - Residual Cancer burden as a prognostic factor in a large series of Neoadjuvant chemotherapy. Subgroup analysis per molecular surrogated subtypes
Presenter: Catalina Falo
Session: Poster Display session 2
Resources:
Abstract
5014 - Clinical validation of CanAssist Breast in a Spanish cohort
Presenter: Manjiri Bakre
Session: Poster Display session 2
Resources:
Abstract
2787 - Meta-analysis on association of pathological complete response with long-term survival outcomes in triple-negative breast cancer
Presenter: Peter A. Fasching
Session: Poster Display session 2
Resources:
Abstract
4301 - Immune infiltrate composition across intrinsic subtypes in hormone receptor (HR)+/HER2- early breast cancer (BC) enrolled in the prospective LETLOB trial
Presenter: Gaia Griguolo
Session: Poster Display session 2
Resources:
Abstract
3205 - Frequency of germline mutations in women's cancer susceptibility genes in a large cohort of Chinese breast cancer patients
Presenter: Ning Liao
Session: Poster Display session 2
Resources:
Abstract
4091 - Triple blinded Prospective Study assessing the Impact of Genomics & Artificial Intelligence Watson For Oncology (WFO) on MDT’s Decision of Adjuvant Systemic Therapy for Hormone Receptor Positive Early Breast Carcinoma-
Presenter: Somashekhar Sampige Prasannakumar
Session: Poster Display session 2
Resources:
Abstract
4359 - Prognostic significance of Progesterone Receptor levels in luminal-like Her2- early Breast Cancer patients. A retrospective single Cancer Center analysis.
Presenter: Anna Diana
Session: Poster Display session 2
Resources:
Abstract
1369 - PAM50 HER2-enriched subtype and pathological complete response in HER2-positive early breast cancer: a meta-analysis
Presenter: Francesco Schettini
Session: Poster Display session 2
Resources:
Abstract
1058 - Assessment of CPS+EG, Neo-Bioscore and modified Neo-Bioscore in breast cancer patients treated with preoperative systemic therapy: a multicenter cohort study
Presenter: LING XU
Session: Poster Display session 2
Resources:
Abstract